HGS

hepatocyte growth factor-regulated tyrosine kinase substrate, the group of Zinc fingers FYVE-type|ESCRT-0|MicroRNA protein coding host genes

Basic information

Region (hg38): 17:81683326-81703138

Links

ENSG00000185359 ∙ NCBI:9146 ∙ OMIM:604375 ∙ HGNC:4897 ∙ Uniprot:O14964 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HGS gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HGS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	3	6
missense			38	3	1	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding		1	5	1	2	9
Total	0	1	43	7	6

Variants in HGS

This is a list of pathogenic ClinVar variants found in the HGS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-81683555-G-T		not specified	Uncertain significance (Nov 29, 2021)
17-81683716-G-A		not specified	Uncertain significance (Feb 05, 2024)
17-81683735-C-G		not specified	Uncertain significance (Mar 25, 2024)
17-81683746-A-G		not specified	Uncertain significance (Feb 15, 2023)
17-81683756-C-T		not specified	Uncertain significance (Dec 18, 2023)
17-81683773-G-T		not specified	Uncertain significance (Aug 02, 2021)
17-81683794-C-A		Childhood-onset schizophrenia	Likely pathogenic (Jan 01, 2014)
17-81686350-A-C		not specified	Uncertain significance (Aug 02, 2023)
17-81686994-C-T			Benign (Jul 06, 2018)
17-81687042-C-T		not specified	Uncertain significance (Feb 10, 2022)
17-81687055-C-G		not specified	Uncertain significance (Nov 09, 2023)
17-81688716-G-T		not specified	Uncertain significance (Jun 27, 2023)
17-81688776-G-A		not specified	Uncertain significance (Dec 20, 2023)
17-81690173-T-C			Likely benign (Jun 04, 2018)
17-81691447-C-T			Uncertain significance (Apr 01, 2023)
17-81693538-T-G		not specified	Uncertain significance (Sep 12, 2023)
17-81693549-T-C		not specified	Uncertain significance (May 30, 2023)
17-81693553-T-C		not specified	Uncertain significance (Mar 01, 2024)
17-81693560-C-A		not specified	Uncertain significance (Aug 17, 2021)
17-81693564-C-A		not specified	Uncertain significance (Dec 27, 2023)
17-81693571-A-C		not specified	Uncertain significance (Jan 03, 2024)
17-81693574-A-C		not specified	Uncertain significance (Jan 20, 2023)
17-81693579-C-G			Likely benign (Jul 20, 2018)
17-81693660-C-G		not specified	Uncertain significance (Aug 16, 2022)
17-81693880-C-T		not specified	Uncertain significance (Sep 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HGS	protein_coding	protein_coding	ENST00000329138	22	19813

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00636	0.994	125717	0	29	125746	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.28	404	484	0.836	0.0000314	5004
Missense in Polyphen		226	281.32	0.80334		2876
Synonymous	-2.69	269	218	1.23	0.0000167	1493
Loss of Function	4.45	13	45.4	0.287	0.00000203	516

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000420	0.000419
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000110	0.000109
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.0000710	0.0000703
Middle Eastern	0.000110	0.000109
South Asian	0.0000655	0.0000653
Other	0.000332	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down- regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. May contribute to the efficient recruitment of SMADs to the activin receptor complex. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation.
• Pathway: Endocytosis - Homo sapiens (human);Phagosome - Homo sapiens (human);TGF-Ncore;TGF-beta Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;EGF-EGFR Signaling Pathway;Lysosome Vesicle Biogenesis;Clathrin derived vesicle budding;Disease;trans-Golgi Network Vesicle Budding;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Endosomal Sorting Complex Required For Transport (ESCRT);Metabolism of proteins;TCR;Infectious disease;Fibroblast growth factor-1;EGFR downregulation;Signaling by EGFR;Clathrin-mediated endocytosis;TGF_beta_Receptor;EGFR1;CXCR4-mediated signaling events;Ub-specific processing proteases;Posttranslational regulation of adherens junction stability and dissassembly;Deubiquitination;Cargo recognition for clathrin-mediated endocytosis;Negative regulation of MET activity;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Internalization of ErbB1;Signaling events mediated by VEGFR1 and VEGFR2;InlB-mediated entry of Listeria monocytogenes into host cell;Listeria monocytogenes entry into host cells (Consensus)

Recessive Scores

• pRec: 0.383

Intolerance Scores

• loftool: 0.445
• rvis_EVS: -1.5
• rvis_percentile_EVS: 3.6

Haploinsufficiency Scores

• pHI: 0.440
• hipred: Y
• hipred_score: 0.695
• ghis: 0.593

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hgs
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); muscle phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: protein targeting to lysosome;signal transduction;negative regulation of cell population proliferation;membrane invagination;positive regulation of gene expression;negative regulation of platelet-derived growth factor receptor signaling pathway;endosomal transport;macroautophagy;negative regulation of angiogenesis;negative regulation of vascular endothelial growth factor receptor signaling pathway;multivesicular body assembly;negative regulation of epidermal growth factor receptor signaling pathway;regulation of protein catabolic process;regulation of MAP kinase activity;negative regulation of JAK-STAT cascade;membrane organization;protein localization to membrane;positive regulation of exosomal secretion
• Cellular component: lysosome;endosome;early endosome;cytosol;early endosome membrane;multivesicular body membrane;ESCRT-0 complex;intracellular membrane-bounded organelle;extracellular exosome
• Molecular function: protein binding;protein domain specific binding;ubiquitin-like protein ligase binding;metal ion binding